Volume 11 | Issue 5
William Levis MD|No abstract details for the moment.
Ritu Saini MD|No abstract details for the moment.
Treatment of Actinic Keratoses With 5% Topical Imiquimod: A Multicenter Prospective Observational Study from 93 Austrian Office-based Dermatologists
Background: While randomized, controlled trials have generated information about the safety and efficacy of imiquimod 5% cream in the treatment of actinic keratosis, still very little is known about the challenges and pitfalls of this therapy in the daily clinical routine.
Objective: To mirror the full picture of the actinic keratosis imiquimod routine therapy, ie, patient profile, in-therapy decisions, tolerability, and satisfaction.
Methods: The present observational, multicenter study included 463 patients from the offices of 93 non-hospital based Austrian dermatologists. Inclusion was solely based on the treatment decision of the dermatologist and the patient's will to participate. There were no specific interventions except suggested time points of visits with pre-defined documentation forms.
Results: The typical actinic keratosis patient was a male, aged 74 years, with a disease history of 5.7±5.3 years, who presented with 8.4±8.0 multiple pre-treated lesions at the face. More than 95% of the patients developed therapeutic skin responses (dominated by erythema and crusting), which led to a significant reduction of lesions from baseline to the end of the therapy. Notably, one-third of those patients prone to a second therapeutic course were submitted to another form of treatment. Post-imiquimod therapy comprised of antibiotic creams, topical steroids, and numerous emollients. Patients and dermatologists reported high satisfaction with the therapy including the cosmetic outcome.
Conclusion: Our data show the high need for experience at the dermatologist side and information at the patient side. Moreover, the method of treatment for imiquimod-related skin reactions definitively asks for standardization.
The study was registered at ClinicalTrials.gov (NCT01151956). Decision by ClinicalTrials.gov: Federal University Teaching Hospital, Feldkirch, Austria Protocol Record OBIMQ465-AK-08, Imiquimod and actinic keratoses: an observational study.
J Drugs Dermatol. 2012;11(5):574-578.
Objective: To evaluate trends and identify deficiencies and disparities in primary skin cancer prevention efforts among Hispanics in the US.
Methods: PubMed/MEDLINE and SCOPUS were searched using the following keywords: awareness, knowledge, behavior, sunscreen, hat, clothing, minorities, ethnic skin, Hispanic, Latino, and skin. Reference lists of selected studies were checked for additional studies. Studies that quantitatively evaluated primary skin cancer prevention efforts among US Hispanics were selected. Primary outcome measures included 1) use of sunscreen or sunblock, 2) use of sun-protective clothing and/or hats, and 3) shade seeking behavior. Selected studies were reviewed and quantitative data for each primary outcome measure were extracted. Additionally, we examined survey methodology and demographics of the studied populations.
Results: Studies evaluating primary prevention of skin cancer among US Hispanics are limited in number and study populations. Overall, 9.5-29.9% of the Hispanics evaluated reported wearing sunscreen either most of the time or always compared to 16.5-35.9% of NHW. Hispanics reported slightly higher rates of wearing hats compared to NHW, with 23.9-25.0% of Hispanics reporting wearing hats either most of the time or always compared to 20-20.7% of NHW. Trends in wearing sun protective clothing and shade seeking varied between different Hispanic populations evaluated, but overall prevalence of these practices remained low.
Conclusion: The limited studies suggest that improvements are needed in primary skin cancer prevention practiced by Hispanics. Future studies and interventions need to account for heterogeneity in socio-cultural backgrounds, degree of acculturation, and occupation among US Hispanics.
J Drugs Dermatol. 2012;11(5):580-586.
In Vitro PLK1 Inhibition by BI 2536 Decreases Proliferation and Induces Cell-Cycle Arrest in Melanoma CellsMelanoma is one of the most treatment-resistant malignancies and regardless of new therapeutic tactics the outcome remains dismal. Polo-like kinase 1 (PLK1) has been shown to be over-expressed in a variety of tumors, becoming an attractive target for cancer management. In the present study we tested the in vitro antitumor activities of BI 2536, a selective inhibitor of PLK1, against two melanoma cell lines. Our results showed that nanomolar concentrations (10-150 nmol/L) of the drug significantly decreased cell proliferation and clonogenicity, promoting cell cycle arrest in G2/M. Targeting the cell cycle offers an attractive potential cancer-treatment option. Herein we show that PLK1 inhibition may be a feasible approach for the impairment of tumor progression and dissemination. This in vitro profile of melanoma cell growth inhibition by PLK1 modulation may be an interesting model to be tested in association with first-line antineoplasic agents in melanomas.
J Drugs Dermatol. 2012;11(5):587-592.
Evaluation of the Chemopreventative Effects of ALA PDT in Patients With Multiple Actinic Keratoses and a History of Skin CancerBackground: Actinic keratoses (AKs) are in situ epidermal tumors that may progress to invasive squamous cell carcinomas (SCCs). Aminolevulinic acid with photodynamic therapy (ALA PDT) is a field treatment for AK.
Objective: To evaluate the time to development of new non-melanoma skin cancers (NMSC) within one year of ALA-PDT treatment in immunocompetent patients with AK and a history of skin cancer.
Methods and Materials: One hundred forty anatomic sites in 114 patients were treated with topical ALA for a 1 to 3 hour incubation period followed by photodynamic therapy (PDT) with a blue light. All new NMSCs within the treatment areas were recorded over a 1-year observational period.
Results: Eighty-three anatomic sites (59%) did not develop new skin cancers within 1 year. Additionally, 92%, 78%, and 64% of anatomic sites were free of new skin cancers at 3, 6, and 9 months after treatment was initiated. Although approximately 41% of patients treated on both the scalp and face developed new skin cancers within 1 year of treatment, the average time to develop skin cancer was longer for the face (7.09 months) than for the scalp (5.34 months).
Conclusion: In patients with a history of NMSC and multiple AKs, ALA PDT may be a valuable option for the prevention and delay of new NMSCs.
J Drugs Dermatol. 2012;11(5):593-597.
Diclofenac Sodium 3% Gel for the Management of Actinic Keratosis: 10+ Years of Cumulative Evidence of Efficacy and Safety
George M. Martin MDa and Eggert Stockfleth MD PhDb|
Background: Diclofenac sodium 3% gel (Solaraze®) gained US approval for the treatment of actinic keratosis (AK) more than 10 years ago. Since the publication of the pivotal phase 3 studies, numerous clinical studies have assessed use of this therapy in a variety of body areas, special populations, and novel combinations.
Objective: To provide a comprehensive update on clinical data and research on the use of diclofenac sodium 3% gel in AK.
Results: Accumulating evidence from preclinical research supports that the proposed mechanism of diclofenac sodium 3% gel may include cyclo-oxgenase 2 (COX-2) inhibition, inhibition of angiogenesis, and induction of apoptosis. A literature review identified 17 publications (beyond the 2 pivotal studies) on the use of diclofenac sodium 3% gel for AK. A phase 4 open-label study reported that 58 percent of patients achieved complete clearance of target lesions at the 30-day post-treatment assessment; among patients who were evaluable at 1-year post-treatment, sustained long-term clearance of AK lesions was observed. Active comparator studies demonstrated comparable efficacy of diclofenac sodium 3% gel with 5-fluorouracil 5% and imiquimod 5%. Publications on the efficacy of diclofenac sodium 3% gel for AK of the lip report complete clearance rates comparable to those reported for other body areas. Diclofenac sodium 3% gel has also demonstrated efficacy for clearing AK lesions in immunosuppressed populations. Sequential use of diclofenac sodium 3% gel with cryosurgery or photodynamic therapy has been investigated and may emerge as a useful approach for some patients.
Conclusions: Diclofenac sodium 3% gel has a unique proposed mechanism of action in AK that may involve COX-2 inhibition, inhibition of angiogenesis, and induction of apoptosis. In the past decade, numerous clinical studies have demonstrated this topical therapy to be effective and well tolerated for the treatment of AK.
J Drugs Dermatol.2012;11(5):600-608.
Background: Tumor necrosis factor inhibitors are valuable tools for dermatologists. As their use increases, rare adverse events are more likely to be encountered.
Objective: We describe one patient who developed sarcoidosis while being treated for psoriasis with etanercept. We sought to review to previously reported cases and further characterize the nature of this reaction.
Methods: A literature search was performed with the key words "sarcoidosis, sarcoid, etanercept, infliximab, adalimumab, granulomatous, and drug reaction." All relevant cases in the English language were included and evaluated for demographic data, duration of therapy prior to developing sarcoid, duration of sarcoid signs/symptoms, treatments used and time to resolution after discontinuation of the drug.
Results: Including the present case, there are 34 cases of sarcoidosis developing during anti-tumor necrosis factor therapy. All previously reported cases were patients with a primarily rheumatologic diagnosis. In all but one case, discontinuation of the drug resulted in complete resolution of symptoms. The lung and surrounding lymph nodes were the areas most commonly affected. The average amount of time between initiation of therapy and onset of symptoms was 22 months. The average time to resolution of symptoms after discontinuation of the drug was 5.2 months.
Limitations: This is a retrospective case review.
Conclusions: These data indicated that sarcoid is a possible adverse effect of tumor necrosis factor inhibitor therapy that should be noted by dermatologists using these drugs. While it has been reported in the rheumatology literature, it may be under-recognized by dermatologists.
J Drugs Dermatol. 2012;11(5):609-612.
Improved Texture and Appearance of Human Facial Skin After Daily Topical Application of Barley Produced, Synthetic, Human-like Epidermal Growth Factor (EGF) Serum
A three month, open-label, single center study was conducted to determine whether a uniquely derived serum containing barley bioengineered, human-like epidermal growth factor protein could improve visible signs of photodamage and aging in facial skin. Twenty-nine females, aged 39 to 75 years, with mild to severe, fine and course rhytids, photodamage, and pigmentation were enrolled. Subjects then applied the treatment serum per the prescribed protocol twice-daily for 3 months, in addition to the use of a basic sunscreen and facial cleanser. In-person clinical evaluations and subject self-assessment questionnaires were administered at each follow up visit. In addition, clinical photography was completed at baseline, and each subsequent visit. Clinical evaluations showed statistically significant improvement in the appearance of fine lines and rhytids, skin texture, pore size, and various dyschromatic conditions apparent within the first month of use, and continuing improvement trends for the duration of the study. The treatment serum was well tolerated with minimal treatment-related complications reported throughout. Efficacy of this novel serum and treatment protocol resulted in meaningful improvements in photodamage and visible signs of aging.
J Drugs Dermatol. 2012;11(5):613-620.
We propose rituximab as a first-line therapy for pemphigus vulgaris and steroid-dependent bullous pemphigoid with or without systemic steroids. A brief review of the literature substantiates the significant risk associated with the use of long term, high-dose prednisone, mycophenolate mofetil (MMF), and azathioprine. No head-to-head studies are available with respect to safety and efficacy of rituximab versus these therapies. When comparing the side effects of rituximab to MMF, both are found to be mild when used as monotherapy in dermatologic patients. The most severe side effects of rituximab include fatal infusion reactions and hypersensitivity, pancytopenia, infection and organ dysfunction. With MMF, malignancy, pancytopenia, infection, and organ dysfunction are the most concerning side effects. The frequencies of these observed adverse events are difficult to compare, but the side effect profiles of rituximab and MMF are clearly similar. Therefore, there is equipoise whether to use rituximab before rather than after MMF and/or systemic corticosteroids.
J Drugs Dermatol. 2012;11(5):622-625.
Lessons of Leprosy: The Emergence of TH17 Cytokines During Type II Reactions (ENL) Is Teaching Us About T-cell Plasticity
Background: Leprosy was the first disease classified according to the thymus derived T-cell in the 1960s and the first disease classified by the cytokine profile as intact interferon-γ(IFN-γ) and interleukin-2 (IL2) or TH1 (tuberculoid) and deficient IFN-γ and IL2 or TH2 (lepromatous), in the 1980s.
Objective: In the present study, we set out to explore the T helper 17 (TH17) lymphocyte subset, the hallmark of T-cell plasticity, in skin biopsies from patients with erythema nodosum leprosum (ENL) who were treated with thalidomide.
Method: RNA was extracted from paraffin embedded tissue before and after thalidomide treatment of ENL and RT-PCR was performed.
Results: IL17A, the hallmark of TH17, was consistently seen before and after thalidomide treatment, confirming the TH17 subset to be involved in ENL and potentially up-regulated by thalidomide.
Conclusion: A reduction in CD70, GARP, IDO, IL17B (IL-20), and IL17E (IL-25) , coupled with increases in RORγT, ARNT, FoxP3, and IL17C (IL-21) following thalidomide treatment, opens the door to understanding the complexity of the immunomodulatory drug thalidomide, which can operate as an anti-inflammatory while simultaneously stimulating cell-mediated immunity (CMI). We conclude that TH17 is involved in the immunopathogenesis of ENL and that thalidomide suppresses inflammatory components of TH17, while enhancing other components of TH17 that are potentially involved in CMI.
J Drugs Dermatol. 2012;11(5):626-630.
A Comparison of Physicochemical Properties of a Selection of Modern Moisturizers: Hydrophilic Index and pHObjective: To quantify and compare the physiochemical properties of various topical emollients and to correlate these findings with the products' potential to maintain the stratum corneum (SC) acid milieu, while possessing the appropriate water content for skin rehydration, user adherence, and comfort.
Material and Methods: The pH and hydrophilic fraction of 31 skin moisturizers sold in the US were measured. Hydrophilic Index (HI) was calculated using the "HI equation." The two parameters were charted using a scatter plot with quadrant divisions. Products with lower hydrophilicity were considered "more greasy" and assigned a lower HI as compared to their counterparts with a higher hydrophilicity.
Results: Our findings are in good accordance with common clinical impressions: lotions generally have higher HI, while ointments have lower HI. The majority of the products tested fall into low HI, suggesting that a large percentage of the products may be rich in overall lipid content. The pH values range widely, from 3.7 to 8.2, with the majority of the products close to the physiologic skin pH of 4 to 6.
Conclusion: This study introduces HI as a novel method of quantifying the aqueous content of topical emollients. When considered together with pH, the two indices can guide providers in choosing the most suitable emollients for patients with skin diseases involving altered acid mantle and barrier disruption, such as atopic dermatitis, irritant contact dermatitis, and ichthyosis vulgaris.
J Drugs Dermatol. 2012;11(5):633-636.
Biophysical Evaluation of Fractional Laser Skin Resurfacing With an Er:YSGG Laser Device in Japanese Skin
Background: Ablative fractional laser skin resurfacing (FLSR) has recently been used for the amelioration of acne scars, and previous studies have shown clinical effectiveness. Despite its extensive use, few studies have focused on the associated changes in biophysical properties of the epidermis. Herein, we evaluate transepidermal water loss, sebum levels, skin hydration, and skin elasticity, following FLSR treatments with an Er:YSGG laser device (Pearl FractionalTM , Cutera Inc., Brisbane, CA), employing non-invasive measurements.
Methods: Five Japanese patients with facial acne scars underwent one FLSR session. Some acne scars appeared to become less obvious as a consequence of the treatment. All patients were aware of a feeling of skin tightness in treated areas.
Results: Objective measurements on the lower lateral angle of the eye and on the inner cheeks were evaluated at baseline and at 3 days, 1 week, and 4 weeks after FLSR. Transepidermal water loss showed a significant two-fold (100%) increase at day 3, but had returned to almost the baseline level at week 4 in both areas. Sebum secretion showed a 50% increase at day 3, but had returned to the baseline level after day 7. Skin hydration showed a significant decrease at day 3, but had returned to the baseline level by day 7, and showed significant improvement at the end of the study. Skin elasticity (R2) was still at baseline on day 3, but showed some improvement—an increase of at least 30%—at the end of the study.
Conclusions: Based on our findings, we believe that FLSR should be performed no more than once a month to allow sufficient time for the damaged skin to recover its barrier function in most areas of the face.
J Drugs Dermatol. 2012;11(5):637-642.
Fitzpatrick Skin Types and Clindamycin Phosphate 1.2%/Benzoyl Peroxide Gel: Efficacy and Tolerability of Treatment in Moderate to Severe Acne
Background: Acne in skin of color is an increasing problem, presenting unique challenges. Although combination therapy is now standard of care in acne, concerns exist with the increased potential irritation and dryness in skin of color. Although individual medications can be titrated or applied at different times of the day to minimize irritation, this is not always practical or desirable. There is a paucity of clinical studies that evaluate the safety and efficacy of acne medications in skin of color.
Methods: A post-hoc analysis of efficacy and cutaneous tolerability in 797 subjects receiving clindamycin phosphate 1.2% benzoyl peroxide (BPO) 2.5% gel from two 12-week, multi-center, double-blind studies that enrolled 2,813 subjects with moderate to severe acne. Efficacy, tolerability, and subject satisfaction in Fitzpatrick skin types I-III subjects were compared to subjects with Fitzpatrick skin types IV-VI.
Results: Median reductions in inflammatory lesions were comparable between the two groups. There was a small difference in non - inflammatory and total lesions in favor of those patients with Fitzpatrick skin types I-III (P=0.013 and P=0.024, respectively). Median reductions in inflammatory, noninflammatory, and total lesions at week 12 were 63%, 50%, and 52.4%, respectively for Fitzpatrick skin types I-III and 65%, 47%, and 51.4%, respectively for Fitzpatrick skin types IV-VI. Treatment success was comparable between the two groups and both groups had a high level of subject satisfaction at week 12. Cutaneous tolerability was excellent, with all mean scores less than or equal to 0.2 at week 12 (where 1=mild). Results in the two groups were comparable, although there was slightly more erythema reported in the Fitzpatrick skin types I-III subjects (0.2 versus 0.1). This could be due to the difficulty in vis ualizing erythema in subjects with darker skin.
Conclusions: Acne subjects with Fitzpatrick skin types IV-VI were not found to be more susceptible to cutaneous irritation from treatment with clindamycin phosphate 1.2%/BPO 2.5% gel and both efficacy and tolerability was comparable across the two treatment groups.
J Drugs Dermatol. 2012;11(5):643-648.
Background: Upper lip wrinkling is a common complaint of patients seeking perioral rejuvenation. Lately, manual dermabrasion has become more popular due to its safety, minimal cost, and favorable results. In several hospitals, the ability to efficiently ste rilize sand paper has been questioned.
Methods: Between 2007 and 2010, 29 patients underwent manual dermabrasion of the skin of the upper lip using an electric cautery scratch pad during their surgeries.
Results: The average patient was aged 60.2 years. The average healing period was 5.8 days. Patient satisfaction from the procedure ranged from very good to excellent. No serious or long lasting complications have been encountered during our follow-up period.
J Drugs Dermatol.2012;11(5):649-652.
Elizabeth Gaines-Cardone MD and Elizabeth K. Hale MD SUNY Downstate Department of Dermatology, Brooklyn, NY|Immunosuppression is a known risk factor for the development of non-melanoma skin cancers (NMSC). Certain medications that induce immunosuppression, such as tumor necrosis factor-α (TNF-α) inhibitors, are being used more frequently. We report a case of a young, pregnant woman who was treated with infliximab for Crohn's disease, and subsequently experienced a rapid growth of two pre-existing basal cell carcinomas. As use of TNF-α inhibitors increases, it is important to closely monitor patients for the development of NMSC.
J Drugs Dermatol. 2012;11(5):655-656.
Background: Melasma is a cutaneous disorder associated with an overproduction of melanin by the tyrosinase enzyme. A proprietary oligopeptide (Lumixyl TM ) was previously shown to competitively inhibit mushroom and human tyrosinase in vitro without the associated cytotoxicity of hydroquinone and to diminish the appearance of facial melasma.
Objective: The aim of this case study was to determine if the Lumixyl Topical Brightening System (0.01% oligopeptide cream, an antioxidant cleanser, 20% glycolic acid lotion and physical sunscreen) accelerates clearance of mild-to-moderate melasma.
Results: All patients showed improvement in their facial melasma with 1 of 4 patients showing complete clearance after just 6 weeks.
Conclusions: Results suggest that this regimen may be a useful new tool to treat mild to moderate melasma.
J Drugs Dermatol.2012;11(5):660-662.
RESIDENT ROUNDS: PART I
Program Spotlight: Department of Dermatology,Oregon Health & Science UniversityResident Rounds is a section of the JDD dedicated to highlighting various dermatology departments with residency training programs. Resident Rounds includes three sections: (1) a program spotlight, highlighting pertinent information about the department and residency training program; (2) a section presenting study materials used by residents at the program; and (3) a section designed to highlight recent interesting cases seen at the institution. This issue of Resident Rounds features the Department of Dermatology, Oregon Health & Science University. The editor of Resident Rounds is Omar A. Ibrahimi MD PhD. He is currently the Director of Cutaneous Laser and Cosmetic Surgery and a Mohs surgeon at the University of Connecticut. Dr. Ibrahimi is also a Visiting Scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital/Harvard Medical School. If you are interested in highlighting your training program in a future issue, please contact Dr. Ibrahimi at OIbrahimi@jddonline.com.
No abstract details for the moment.
No abstract details for the moment.
Anne Chapas MD FAAD and Kendra Gail Bergstrom MD FAAD|No abstract details for the moment.
Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.
Clinical Trial Review is a JDD department designed to provide physicians with information on drugs and devices undergoing clinical testing. It is our goal to inform the reader of the status of select drug and device studies relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.
Leon H. Kircik MD, Neh Onumah MD, Joshua A. Zeichner MD, Elena Sotiriou MD PhD, Christina Goussi MD, Aimilios Lallas MD, Eleni Chovarda MD, Zoe Apalla MD, Elisabeth Lazaridou MD PhD, Demetris Ioannides MD PhD|This supplement to the Journal of Drugs in Dermatology help address various components of psoriasis and comorbidities, as well as hidradenitis suppurativa and biologic treatments. Dr. Kircik and Onumah's article covers psoriasis and its identified comorbidities or chronic proinflammatory disorders driven by similar immunopathologic expression of immune response mechanisms. Dr. Zeichner covers immunologic therapies for treatment of psoriasis-tumor necrosis factor (TNF) inhibitors and interleukin (IL)-12 and IL-23 inhibitors: etanercept, adalimumab, infliximab, golimumab, and ustekinumab. Dr. Zeichner also considers therapeutic management prior to initiating biologic therapy. Lastly, Drs. Elena Sotiriou MD PhD et al from Aristotle University in Thessaloniki, Greece provides perspectives on a prospective clinical trial of efficacy of adalimumab in the treatment of hidradenitis suppurativa. The study demonstrates the significant efficacy of the once weekly regimen, as well as its benefit regarding time to recurrence.